B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients

Emiliano Marasco, Chiara Farroni, Simona Cascioli, Valentina Marcellini, Marco Scarsella, Ezio Giorda, Eva Piano Mortari, Lucia Leonardi, Alessia Scarselli, Diletta Valentini, Caterina Cancrini, Marzia Duse, Ola Grimsholm, Rita Carsetti

Research output: Contribution to journalArticlepeer-review

Abstract

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.

Original languageEnglish
Pages (from-to)131-143
Number of pages13
JournalEuropean Journal of Immunology
Volume47
Issue number1
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • Journal Article

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